Podium Presentation Animal Models

18.3.10 - Osteochondritis Dissecans Chondrocytes: A Novel Source for Cartilage Tissue Engineering

Presentation Number
18.3.10
Presentation Topic
Animal Models
Lecture Time
15:36 - 15:45
Session Type
Free Papers
Corresponding Author
  • L. Moncada-Palazuelos (Davis, US)
Authors
  • L. Moncada-Palazuelos (Davis, US)
  • V. Krasnodemsky (Davis, US)
  • O. Sayfan (Davis, US)
  • A. Kapatkin (Davis, US)
  • B. Filliquist (Davis, US)
  • P. Chou (Davis, US)
  • D. Marcellin-Little (Davis, US)
  • N. Vapniarski-Arzi (Davis, US)
Disclosure
No Significant Commercial Relationship

Abstract

Purpose

Osteochondritis dissecans (OCD) is the result of abnormal development of cartilage leading to joint disease across many species including dogs. Surgical treatment is palliative and includes removal of the detached cartilage fragment. These fragments contain viable chondrocytes and can serve as a unique cell-source for cartilage tissue engineering. The purpose of this study is to prove that a novel scaffold-free approach can yield neocartilage tissue with properties akin to native cartilage.

Methods and Materials

icrs abstract m&m.png

OCD fragments are enzymatically digested and matrix-free chondrocytes are expanded for 2-3 passages. The cells are then transferred onto a no-adherent bioreactor suspension culture for 10 days where cells form spherical aggregates. Single cells obtained by enzymatic digestion of aggregates are then seeded at high density into custom-made agarose molds where a process of self-assembling materializes. In this process, chondrocytes coalesce and generate tissue-specific extracellular matrices (ECM) such as glycosaminoglycans and collagen. During the construct maturation period of 4 weeks, both mechanical and biological stimuli are introduced in a consecutive, simultaneous and synergistic fashion. Constructs are collected on day 28 of seeding and subjected to mechanical and biochemical testing.

Results

figure 2 icrs aprill 15 2019.png

Our methods yielded dozens of 0.8x1.4cm cartilage constructs from one 0.3mm in diameter OCD fragment. The biomimetic index that reflects the overall mechanical and biochemical properties of the engineered construct relative to native tissue was 88%. The compressive and tensile stiffness of engineered cartilage was 501kPa and 2.3MPa, respectively. The glycosaminoglycan content was 26.4%/DW and collagen 6.0%/DW.

Conclusion

The high degree of biomimicry achieved by this study without the use of exogenous scaffolds holds promise for clinical translation. The custom-made agarose molds that define the shape and size of these scaffold-free constructs can be tailored to individual patient needs using 3D printing technology. Lastly, demonstrating the feasibility of this approach in a naturally-occurring canine disease-model offers an additional translational advantage.

Collapse